Serum albumin is the most abundant protein in blood plasma, and its biological functions include binding and transporting a series of endogenous and exogenous substances as well as maintaining normal blood osmotic pressure and so on. In recent years, human serum albumin (HSA) as a drug carrier has received extensively attention. HSA consists of 585 amino acid residues, has a molecular weight of about 66 kD, and also has advantages of safety without toxicity, good biocompatibility and so on.
There are two main ways of carrying drugs by albumin: the first way is that the drug and albumin are linked by molecular chains, that is, formation of albumin-drug conjugate using chemical coupling; the second way is to rely on the interaction between drug and albumin to achieve drug embedding, that is, carrying drug by albumin using physical binding, which can improve the solubility and stability of the drug.
The current study for HSA drug carrier is mainly aimed at anti-tumor drug. Physical embedding effect of drugs carried by HSA is achieved by the physical binding of HSA, such as hydrophobic, electrostatic and other interactions to embed and carry drugs, which is capable of improving the stability and targeting ability of the drug and has sustained release effects. Therefore, HSA can be used as an ideal drug carrier for new type of complexes of peptide drugs.
Tumors are a class of diseases which impose a serious threat to people's health. Tumors can be divided into benign tumors and malignant tumors, and the main difference between the two is that the malignant tumors have characteristics of metastasis and recurrence. Tumor metastasis is a sign of poor prognosis, and is also the leading cause of death of a tumor patient.
Chemokines are a class of small single-stranded small molecular proteins that, by interaction with G-protein-coupled receptors, cause cytoskeletal rearrangement of target cells, and to adhere to endothelial cells firmly and directionally migrate. In recent years, domestic and foreign studies have showed that stromal cell-derived factor-1 (SDF-1), i.e. chemokine CXCL12, and its specific chemokine receptor CXCR4 play an important role in a variety of organ-specific metastasis of tumor. The specific chemokine receptor CXCR4 is highly expressed on the surface of many solid tumor cells and leukemic cells, while chemokine CXCL12 is highly expressed in bone marrow, lymph nodes and some organs.
Solid tumor cells and leukemic cells highly expressing CXCR4 tend to migrate to some organs such as lungs, bone marrow, etc., as origins of chemokine CXCL12 in a reverse-concentration gradient, forming organ-specific metastases (Balkwill F SeminImmunol, 2003, 15, 49-55). Therefore, targeted inhibition of CXCL12/CXCR4 interaction by using CXCR4 antagonists can block the adhesion of tumor cells and leukemia cells to stromal cells, increase the sensitivity of tumor cells and leukemic cells to chemotherapeutic drugs, and prevent the metastasis and recurrence of tumor as well as leukemia.
Since polypeptides can be easily synthesized, easily metabolized in the human body without toxic side effects and severe immune responses, it is of great importance to develop peptides specifically targeting CXCR4 receptors for inhibiting tumor metastasis and treating leukemia.